Background: The DBCG 77C trial compared one year of tamoxifen in postmenopausal, steroid-receptor unknown, high-risk breast cancer patients to no adjuvant systemic therapy. After a potential follow-up of 30 years we report overall efficacy of the study and results according to subtypes subsequently assessed by immunohistochemistry and fluorescent in situ hybridisation (FISH). Methods: Between 1977 and 1982, 1716 postmenopausal patients with tumours larger than 5 cm or positive axillary nodes were randomly assigned to no systemic therapy or tamoxifen 30 mg daily for one year. Archival tumour tissue from 1515 patients was analysed and the hormone receptor positive (estrogen receptor (ER) and/or progesterone receptor (PR)) cancers were defined as luminal A if Ki67 low and HER2-negative; as luminal B if Ki67 high or HER2-positive; and otherwise as non-luminal-HER2 positive or triple negative. Findings: In the intent-to-treat (ITT) population one year of tamoxifen improved the disease-free-survival (DFS) (hazard ratio (HR) = 0.87; 95% confidence interval (CI) 0.77-0.98), the Breast Cancer Recurrence Rate (BCRR) (HR = 0.79; 0.69-0.90) and reduced the breast-cancer-specific-mortality (BCM) (HR = 0.83; 0.73-0.93). BCRR were improved significantly by tamoxifen in luminal A (HR = 0.66; 0.53-0.84) and luminal B/HER2- (HR = 0.54; 0.39-0.74) but not in the other subsets, and with similar results for BCM with 30 years follow-up. Interpretation: One year of treatment with tamoxifen significantly improves BCRR and BCM in postmenopausal patients with ER positive breast cancers. The relative benefit from tamoxifen was not significantly different in luminal A and B subtypes. Funding: The Danish Breast Cancer Cooperative Group (DBCG) prepared the original protocol (DBCG 77C) and was the sponsor of the study. Funding was not provided to the participating departments. The biomarker study was supported by grants from the Clinical Institute, Odense University. (C) 2014 Elsevier Ltd. All rights reserved.
European Journal of Cancer, 2014, Vol 50, Issue 8, p. 1412-1421
Breast Menopausal Tamoxifen Subtypes Randomised adjuvant phase III trial INTERNATIONAL EXPERT CONSENSUS GROWTH-FACTOR RECEPTOR COOPERATIVE-GROUP DBCG PROGNOSTIC VALUE PREDICTIVE-VALUE PRIMARY THERAPY FOLLOW-UP WOMEN EXPRESSION LETROZOLE; Adult; Aged; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Intention to Treat Analysis; Ki-67 Antigen; Middle Aged; Postmenopause; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Risk Factors; Survival Analysis; Tamoxifen; Treatment Outcome; Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial; Receptor, erbB-2